Alcohol-induced intrauterine growth retardation (IUGR) has long been recognized, yet there remains no biochemical explanation as to the etiology of this abnormality. This proposal aimed at elucidating this mechanism by investigating the relationship of growth factors (GFs) and growth inhibitors (GIs) to normal fetal growth and alcohol-induced IUGR. A miniature swine (Sinclair S-1) is used as an experimental model for this study because of the known alcoholic inclination of these animals. Four serial pregnancies are planned for six alcoholic sows and six alcohol naive controls. Sera from pregnant mother, fetuses and neonates, amniotic fluids at term, and amniotic fluids of mother sows when they are to be sacrificed during the different weeks of the 4th pregnancy, will be evaluated for the levels of epidermal growth factor, transforming growth factors and insulin-like growth factors. Fetal tissues from diagnosed IUGR and normal fetuses will be used to study their ability to synthesize these GFs in vitro. Tissue GF/GI and their membrane cognate receptors will be determined by immunohistochemistry; and their expression in tissues evaluated by in situ hybridization. Both Western and Northern blotting techniques will be employed to characterize these biochemical determinants. This study will yield pertinent information for: (a) the identification of plausible biochemical determinants that may be causual factors for alcohol-induced IUGR, and autocrine/ paracrine factors related to fetal growth, (b) the fitness of the miniature swine as an experimental model for symmetrical IUGR study and (c) the identification of potential markers for IUGR detection. Therefore, this investigation of is fundamental, clinical and potential therapeutic importance.